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Themen
Research
- Focus A
- A01: Targeting tumor cell network communication to overcome primary and adaptive resistance in glioblastoma
- A02: Development of a specific combination therapy for histone H3-mutant pediatric glioblastoma
- A03: Deciphering resistance against targeted treatments
- A04: Elucidating tumor-associated microglia interactions in astrocytomas CNS WHO-grade 4
- A05: Predictive biomarkers for MGMT-promoter-methylated glioblastoma (2019 – 2023)
- A06: Resistance mechanisms of glioblastoma against alkylating agents and radiotherapy
- A07: Mapping and targeting neuron-tumor networks to tackle therapy resistance in glioblastoma
- A08: Personalized glioblastoma treatment guided by patient-derived tumor organoids
Research
- Focus B
- B01: Mechanisms of response and resistance to glioma-specific t cells
- B02: DNA mis-match repair regulates immune checkpoint blockade therapy in glioblastoma (2019 – 2023)
- B03: Targeting immunosuppressive programs in isocitrate dehydrogenase mutant gliomas
- B04: Impact of myeloid cells on the adaptive immune response in newly diagnosed and recurrent glioblastomas
- B05: Dissecting the response of glioblastoma and its tumor microenvironment to focused high-dose radiotherapy (2019 – 2023)
- B06: Visualization and characterization of immune responses in H3K27M mutant gliomas
Research
- Focus C
- C01: Comprehensive preclinical pharmacology testing of drugs used for glioblastoma treatment
- C02: Radiomics, radiogenomics and deep-learning in neurooncology
- C03: Imaging immune signatures of glioma response and resistance towards immunotherapy (2019 – 2023)
- C04: Metabolic signaling in glioblastoma: a spatial multi-omics approach
- C05: Overcoming glioma radio-resistance with particle therapy
- C06: Functional characterization of EGFR structural variants associated with long-term survival in glioblastoma, IDH-WT
PROGNOSTIC MARKERS OF DNA METHYLATION AND NGS SEQUENCING IN PROGRESSIVE GLIOBLASTOMA FROM THE EORTC-26101 TRIAL
RESEARCHResearch findings related to UNITE work package A01/A03/A06/B01/C02/C06
The EORTC-26101 study was a randomized phase II and III clinical trial of bevacizumab in combination with lomustine versus lomustine alone in progressive glioblastoma. Other than for progression-free survival (PFS), there was no benefit from addition of bevacizumab for overall survival (OS). However, molecular data allow for the rare opportunity to assess prognostic biomarkers from primary surgery for their impact in progressive glioblastoma. We analyzed DNA methylation array data and panel sequencing from 170 genes of 380 tumor samples of the EORTC-26101 study. These patients were comparable with the overall study cohort in regard to baseline characteristics, study treatment, and survival. Of patients’ samples, 295/380 (78%) were classified into one of the main glioblastoma groups, receptor tyrosine kinase (RTK)1, RTK2 and mesenchymal. There were 10 patients (2.6%) with isocitrate dehydrogenase mutant tumors in the biomarker cohort. Patients with RTK1 and RTK2 classified tumors had lower median OS compared with mesenchymal (7.6 vs. 9.2 vs. 10.5 months). O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation was prognostic for PFS and OS. Neurofibromin (NF)1 mutations were predictive of response to bevacizumab treatment. Thorough molecular classification is important for brain tumor clinical trial inclusion and evaluation. MGMT promoter methylation and RTK1 classifier assignment were prognostic in progressive glioblastoma. NF1 mutation may be a predictive biomarker for bevacizumab treatment.
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